The mucosal membranes of all humans are naturally colonized by bacterial microflora. Recent studies have indicated that these microflora interact closely with cells and tissues of the body to regulate natural biological processes such as non-specific host defense. See, e.g., Redondo-Lopez, et al. (1990) Rev. Infect. Dis. 12:856-872. Epidemiological evidence suggests that the normal vaginal microbial ecosystem may play a critical role in reducing the risk of sexually transmitted infections, including human immunodeficiency virus-1 (HIV-1). Indeed, depletion of vaginal Lactobacillus is associated with development of clinical syndromes, such as bacterial vaginosis (BV), establishment of opportunistic infections, and an increased risk of acquiring HIV-1 and Herpes simplex virus type 2 (HSV-2) in women. See, e.g., Sha et al. (2005) J. Infect. Dis. 191:25-32; Taha et al. (1998) AIDS 12:1699-1706.
There has been considerable interest in the development of non-antibiotic, ecologically appropriate approaches, such as Lactobacillus Replacement Therapy (LRT) to replenish healthy vaginal flora and to prevent urogenital infections. The vagina, together with its microflora, constitutes a dynamic ecosystem with important host defense capabilities that promote reproductive health. In healthy women of child-bearing age, the vaginal flora is dominated by 10−7-10−9 colony forming units (CFU) of Lactobacillus per gram of fluid. The species of Lactobacillus most commonly isolated from the reproductive tracts of healthy women worldwide includes L. crispatus, L. jensenii, L. gasseri, and L. iners. See, e.g., Antonio et al., (1999) J. Infect. Dis. 180:1950-1956; Vasquez et al., (2002) J. Clin. Microbiol. 40:2746-2749. These species are phylogenetically different from food and/or environmental Lactobacillus species. These facultative anaerobes metabolize glucose to lactic acid, contributing to the maintenance of a low vaginal pH (4.0-4.5) that accounts for a major part of the non-specific defense of the vagina. An acidic pH has a significant antiviral effect against HIV, HSV-2, and other urogenital pathogens. Therefore, beneficial lactobacilli associated with the vaginal mucosa can be considered to provide a protective “biofilm”. See e.g., Falagas et al., (2006) Drugs, 66:1253-1261.
The success of LRT depends in part on selection of an ecologically appropriate Lactobacillus strain, cell preservation, cell recovery of the dried and formulated Lactobacillus following rehydration, as well as the extent and duration of vaginal colonization.
Various methods for administering beneficial bacteria and other substances to the vaginal mucosa are known. For example, dried Lactobacillus have been administered as vaginal tablets, capsules, and as vaginal suppositories. A major drawback of each of these preparations is a low percentage of physiologically viable cells reflected by a low recovery in simulated vaginal fluid, significantly affecting the actual bacterial dosage. The present invention addresses these and other needs.